EFFECT OF MECHANICAL VENTILATION STRATEGY ON DISSEMINATION OF INTRATRACHEALLY INSTILLED ESCHERICHIA-COLI IN DOGS

Objective: To test the effect of different mechanical ventilation stra tegies on dissemination of intratracheally instilled Escherichia coli in dogs and to determine the extent and distribution of lung damage. D esign: Prospective, randomized study. Setting: Experimental animal lab oratory. Subjects: Eighteen anesthetized and paralyzed dogs. Intervent ions: We studied the effect of three ventilatory strategies based on t wo variables: transpulmonary pressure and positive end expiratory pres sure (PEEP). Group 1 animals (n = 6) were ventilated with a PEEP of 3 cm H2O and a tidal volume of 15 mL/kg, which generated an end inspirat ory transpulmonary pressure of less than or equal to 15 cm H2O. In gro up 2 (n = 6), tidal volume was adjusted to generate a transpulmonary p ressure of 35 cm H2O and PEEP was set to 3 cm H2O. In group 3 (n = 6), tidal volume was also adjusted to yield a transpulmonary pressure of 35 cm H2O but PEEP was set to 10 cm H2O. In each group, we instilled s imilar to 10(8) colony-forming units of E. coil into the trachea of th e dogs and ventilated them with the chosen tidal volume and PEEP for 6 hrs afterward. Measurements and Main Results: We measured the pressur e volume relationship (pressure volume curve) of the respiratory syste m before and 6 hrs after bacterial instillation. We obtained blood cul tures before and 0.5, 1, 2, 3, 4, 5, and 6 hrs after bacterial instill ation. After 6 hrs, the lungs were removed for histologic (histologic score) and gravimetric (wet-to-dry weight ratio, WW/ DW) analysis. Dur ing the experiment 0, 5, and 1 dogs developed positive blood cultures in groups 1, 2, and 3, respectively. The number of dogs that developed bacteremia in group 2 was significantly greater than in the other two groups (p < .05). In group 1, pressure-volume curves demonstrated a l ower inflection point which was greater than the end-inspiratory trans pulmonary pressure suggesting that low transpulmonary pressure/low PEE P strategy ventilated aerated regions without expanding atelectatic ar eas. In group 2, presssure-volume curves demonstrated both a lower inf lection point and an upper deflection point which were spanned by the tidal volume, suggesting that high transpulmonary pressure/low PEEP st rategy might have caused both overdistention and cyclic closure and re opening. In group 3, pressure volume curves demonstrated only a upper deflection point which was less than the maximal alveolar tidal pressu re. At the end of the experimental protocol, group 2 manifested the mo st lung injury as assessed by gravimetric and histologic indices of lu ng injury. WW/DW of group 2 (13.1 +/- 1.0 (SD); p < .05) was greater t han groups 1 and 3 (7.5 +/- 1.2 and 8.6 +/- 1.0, respectively). Simila rly, the overall weighted histologic injury score for group 2 (1.19 +/ - 0.26; p < .02) was greater than for groups 1 and 3 (0.82 +/- 0.20 an d 0.88 +/- 0.22, respectively). For groups 2 and 3, the overall weight ed histologic injury scores of the dependent regions were greater than the nondependent regions (p < .004). Conclusions: We conclude that th e ventilatory strategy most likely to overdistend the lungs while allo wing repetitive opening and closure of alveoli (group 2) facilitated b acterial translocation from the alveoli to the bloodstream and increas ed lung injury, as determined by histologic and gravimetric analysis. PEEP ameliorated these effects, despite lung overdistention, but incre ased histologic and gravimetric indices of lung injury in dependent as compared with the nondependent regions.